The H-4 strain of herpes simplex virus was topically administered to the abraded corneas of 36 rabbits. On days 3 through 24, animals were sacrificed, and the preauricular and cervical lymph nodes draining the infected and the contralateral non-infected eyes were removed. Cell suspensions of lymphocytes were prepared from the unilaterally removed nodes, and two cell populations (whole node and whole node depleted of adherent cells) were tested via the lymphocyte transformation assay. Each cell population was tested with optimal concentrations of the T-cell mitogens PHA, PW, and Con A and to specific herpes antigens. Immunosuppression and immunopotentiation of lymphocyte response to mitogens and specific HSV antigens were selective and unique in regional lymph nodes draining infected and non-infected contralateral eyes. In vitro addition of carrageenan to lymphocyte cultures suggested a possible role for macrophages in the immunosuppression/immunopotentiation of lymphocytes in response to mitogens and specific HSV antigens.